PRIMARY REFRACTORY OR RELAPSED NEUROBLASTOMA MedDRA version: 20.0 Level: PT Classification code 10029260 Term: Neuroblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: APN311
Product Code: ch14.18/CHO
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Not yet available
Current Sponsor code: APN311
Other descriptive name: CH
Sponsors
Medical University Greifswald
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Both male and female patients will be considered eligible to enter the study if they satisfy all of the following inclusion criteria: a) = 12 months and = 21 years of age at the time of study entry b) Diagnosis of neuroblastoma according to the INSS criteria c) Tumour burden controlled by conventional therapy (except patients with early minimal bone marrow relapse) fulfilling one of the following criteria: - Primary refractory patients with stage 4 disease - Relapse after primary stage 4 disease - Disseminated relapse after primary localized neuroblastoma. d) Measurable and/or evaluable disease in any of the following sites (skeletal lesions, soft tissue lesions, lymph nodes and/or primary tumour site and/or bone marrow) as measured by mIBG scan, CT, MRI and/or immunocytology e) Life expectancy of at least 12 weeks. f) Performance status greater or equal to 70% (Lansky Score or Karnofsky) g) Consent to the placement of a central venous line, if one has not already been placed h) Off any standard or experimental treatment for at least two weeks prior to start of immunotherapy (Day 1 of cycle 1) and fully recovered from the short-term major toxic effects i) No immediate requirements for palliative chemotherapy, radiotherapy or surgery j) At least 2 weeks from any tumour surgery and fully recovered from any post-surgical complications k) HIV sero-negative l) Neither active nor chronic-replicative Hepatitis B infection m) Females of childbearing potential must have a negative pregnancy test and must agree to use an effective birth control method during the whole study duration including the last FU visit. Female patients who are lactating must agree to stop breast-feeding. n) Patient may have had prior CNS metastases, provided the following criteria are all met: - The patient’s CNS disease has been previously treated. - The patient’s CNS disease has been clinically stable for four weeks prior to starting this study (assessment must be made clinically and by CT or MRI). - The patient is off steroids for four weeks prior to starting trial treatment and will not require them during the course of the study. o) Patients with seizure disorders may be enrolled if well controlled on anticonvulsants and if no seizures have occurred within a 6 week period prior to starting trial Treatment p) All patients and/or their parents or legal guardians must sign a written informed consent. q) Laboratory testing: - Shortening fraction of = 30 % on Echocardiogram. - FEV1 and FVC >60% of the predicted by pulmonary function tests. Children unable to do PFTs should have no dyspnoea at rest and a pulse oximetry >94% in room air. - Adequate bone marrow function as defined by ANC >0.5 10^9/L, platelets 20 10^9/L and haemoglobin > 8.0 g/dL. - Adequate liver function, as defined by an ALT or AST 60 mL/minute/1.73 m2. Are the trial subjects under 18? yes Number of subjects for this age range: 39 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients are NOT eligible for this study if they meet any of the following exclusion criteria: a) Progressive disease at the time of inclusion into the study. b) ADA positivity due to previous treatment with an anti-GD2 antibody (e.g. ch14.18/SP2/0, ch14.18/CHO). c) Previous treatment with ch14.18/CHO in this study d) deleted e) Requirement, or likely requirement, for corticosteroids or other immunosuppressive drugs. f) Concurrent treatment with any non-trial anticancer therapies. g) Patients with hypersensitivity against one component of the investigational product or against mouse proteins. h) Female patients of childbearing potential if pregnant, nursing, or not using effective contraception during the treatment period, as the potential effects of ch14.18 on the fetus have not been determined.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the anti-tumour activity of ch14.18/CHO continuous Infusion in patients with primary refractory or relapsed neuroblastoma.;Secondary Objective: The secondary objectives are to evaluate · Progression-Free Survival · Overall Survival · Safety and tolerability · Pharmacokinetics · Pharmacodynamic activity · Immunogenicity and of ch14.18/CHO continuous infusion in patients with primary refractory or relapsed neuroblastoma.;Primary end point(s): The primary efficacy end point of the study is: · Response rate in patients with measurable/evaluable disease (skeletal lesions, soft tissue lesions, lymph nodes and/or primary tumour site, bone marrow) as measured by mIBG, CT, MRI and/or immunocytology at the end of study;Timepoint(s) of evaluation of this end point: Mid-Evaluation (within 2 weeks before end of cycle 2), end of treatment, 6-weekly follow-up, end of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints of the study are: · Efficacy: => Progression-free survival => Overall Survival · Safety and tolerability: => Pain intensity and pain relief by appropriate medication => Adverse events, vital signs and changes in clinical laboratory assessments · Pharmacodynamic parameters (immunophenotyping, ADCC, CDC, WBT, cytokines) · Immunogenicity (ADA) · Pharmacokinetic parameters;Timepoint(s) of evaluation of this end point: data for the assessment of the secondary endpoints are collected throughout the study. | — |
Countries
Austria, Germany
Contacts
Public ContactHolger Lode
Medical University Greifswald
Outcome results
None listed